Heart failure, often referred to as congestive heart failure (“CHF”) is a major health problem in the United States, affecting about 2% of adults, and about 6 to 10% of adults over the age of sixty-five. The magnitude of heart failure as a clinical problem has emphasized the need to develop new treatment strategies.
Heart failure is a debilitating disease that is generally defined as the inability of the heart to supply sufficient blood flow to the tissues and organs of the body. In some instances, the cardiac output is low, the body becomes congested with fluid. However, fluid overload is not co-terminus with heart failure and some patients may be euvolaemic or dehydrated. The effects of CHF cause the heart muscle to work harder. Over time, increases in workload will produce changes to the heart muscle. In particular, the heart may suffer from reduced force of contraction due to overloading ventricle. Typically, increased filling of the ventricle results in an increased force of contraction and a rise in cardiac output. During heart failure, the ventricle fills with blood but the heart muscle has a reduced ability to cross link actin and myosin fibers over the stretched heart muscle, and consequently, the heart muscle contraction becomes less efficient. Reduced contractility of the heart can cause also reduce stroke volume. Other changes in the heart itself include: loss of one's cardiac reserve, especially during exercise, increased heart rate, which may be stimulated by increased sympathetic activity to maintain cardiac output, arrhythmias, hypertropy (an increase in physical size) of the myocardium, enlargement of the ventricles, contributing to the enlargement and spherical shape of the failing heart. The increase in ventricular volume also causes a reduction in stroke volume due to mechanical and contractile inefficiency.
In chronic heart failure, the reduced cardiac output can cause various changes in the rest of the body, such as decreased arterial blood pressure, increased sympathetic stimulation, which may cause increased secretion of vasopressin, fluid retention and consequently increased blood pressure. Other changes include reduced perfusion to organs such as the kidneys, which may cause secretion of renin, an enzyme that catalyses the production of the vasopressor angiotensin. Angiotensin and its metabolites can cause further vasocontriction, and stimulate increased secretion of aldosterone, which can further promote salt and fluid retention at the kidneys, also increasing the blood volume and blood pressure.
Chronic high levels of hormones such as renin, angiotensin, and aldosterone can negatively affect the myocardium, causing structural remodeling of the heart over the long term. Thus, the maladies of chronic heart failure can be persistent and pervasive.
The National Health and Nutrition Examination Survey (NHANES I) identified the following causes of heart failure: ischemic heart disease, hypertension, valvular heart disease, dilated cardiomyopathy, obesity, and diabetes. The current standards of treatment for heart failure is typically centered on medical treatment using angiotensin-converting enzyme (ACE) inhibitors, diuretics, beta-blockade, and digitalis. Cardiac resynchronization therapy (CRT) may also be employed, if a bi-ventricular pacing device is implanted. New treatments are needed to manage heart failure.